2023 / 02

DOI: 10.24075/medet.2023.016

REVIEW

Ethical issues in pediatric clinical trials

Kolbin AS1,2, Emelianova LI1
About authors

1 Pavlov First Saint Petersburg State Medical University, Saint-Petersburg, Russia

2 St. Petersburg State University, St. Petersburg, Russia

Correspondence should be addressed: Aleksey S. Kolbin
ul. L’va Tolstogo, 6–8, Saint-Petersburg, 197022, Russia; аur.liam@niblok.xel

About paper

Author contribution: Emelianova LI — literature review, writing an article; Kolbin AS — article editing.

Received: 2023-05-29 Accepted: 2023-06-21 Published online: 2023-06-28
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  1. Turner S, Longworth A, Nunn AJ, et al. Unlicensed and off label drug use in paediatric wards: prospective study. British Medical Journal. 1998; 316(7128): 343–5.
  2. Kolbin AS, Zyryanov SK, Belousov DYu. Farmakonadzor. M.: OKI Buki Vedi, 2019; 248 с. Russian.
  3. Saunders H, Wright R, Hodgkin K. Thalidomide and congenital deformities. British Medical Journal. 1962; 2(5307): 796.
  4. Kolbin AS. Clinicheskaya farmacologiya dlya pediatrov: uchebnoe posobie. M.: GEOTAR-Media, 2020; 288 s. Russian.
  5. Shirkey H. Editorial comment: therapeutic orphans. Journal of Pediatrics. 1968; 72: 119–120.
  6. Cohen-Wolkowiez M, Benjamin DK. Development of Therapeutics for Children — A Tricky Balancing Act. JAMA Pediatrics. 2019; 173(1): 18–19.
  7. Green DJ, Sun H, Burnham J, et al. Surrogate Endpoints in Pediatric Studies Submitted to the US FDA. Clinical Pharmacology & Therapeutics. 2019; 105(3): 555–557.
  8. Rieder M, Hawcutt D. Design and conduct of early phase drug studies in children: challenges and opportunities. British Journal of Clinical Pharmacology. 2016; 82(5): 1308–1314.
  9. Yellepeddi VK, Roberts JK, Escobar L, et al. ADME Processes in Pharmaceutical Sciences. Publisher: Springer Cham. 2018; 203–222.
  10. Burckart GJ, van den Anker JN. Neonatal and Pediatric Dose Selection: Quo Vadis? Journal of Clinical Pharmacology. 2021; 61: 7–8.
  11. US National Library of Medicine. Database of privately and publicly funded clinical studies. Available from URL: https://clinicaltrials. gov Date of the application: 05.05.2023.
  12. US Food and Drug Administration. New pediatric labeling information database. Available from URL: https://www.accessdata.fda.gov/scripts/sda/sdNavigation. cfm?sd=labelingdatabase Date of the application: 05.05.2023.
  13. Powell JR, Cook J, Wang Y, et al. Drug Dosing Recommendations for All Patients: A Roadmap for Change. Clinical Pharmacology & Therapeutics. 2021; 109 (1): 65–72.
  14. Garmonizirovannoye trekhstoronneye rukovodstvo ICH. Ukazaniya po doklinicheskim issledovaniyam bezopasnosti v tselyakh provedeniya klinicheskikh issledovaniy na cheloveke i registratsii lekarstv M3 (R2). Tekushchaya versiya (etap 4) ot 11 iyunya 2009 g. Biblioteka normativno-pravovykh aktov. Available from URL: http://pharmadvisor.ru/documents/tr3528/tr3528.html#[6,%22XYZ%22,82,714, null]. Date of the application: 05.05.2023. Russian.
  15. Burt T, Noveck R, MacLeod D, et al. Intra-target microdosing (ITM): a novel drug development approach aimed at enabling safer and earlier translation of biological insights into human testing. Clinical and Translational Science. 2017; 10(5): 337–350.
  16. Turner M, Mooij M, Vaes W, et al. Pediatric microdose and microtracer studies using 14C in Europe. Clinical Pharmacology & Therapeutics. 2015; 98(3): 234–237.
  17. U. S. Department of Health and Human Services, Food and Drug Administration, 21st Century Cures Act FDA, 2018. Available from URL: https://www.fda.gov/Drugs. Дата обращения: 05.05.2023.
  18. U. S. Department of Health and Human Services, Food and Drug Administration, Advisory Committees. Available from URL: www.fda.gov/advisory-committees. Дата обращения: 05.05.2023.
  19. Roth-Cline M, Nelson R. Microdosing studies in children: a US regulatory perspective. Clinical Pharmacology & Therapeutics. 2015; 98(3): 232–233.
  20. Mooij MG, van Duij E, Knibbe CAJ, et al. Successful use of [14C] Paracetamol microdosing to elucidate developmental changes in drug metabolism. Clinical Pharmacokinetics. 2017; 56(10): 1185–1195.
  21. Germovsek E, Barker CIS, Sharland M, et al. Pharmacokinetic-pharmacodynamic modeling in pediatric drug development, and the Importance of standardized scaling of clearance. Clinical Pharmacokinetics. 2019; 58(1): 39–52.
  22. Chitty KM, Chan B, Pulanco CL, et al. Discontinuities and disruptions in drug dosage guidelines for the pediatric population. British Journal of Clinical Pharmacology. 2018; 84(5): 1029–1037.
  23. Rieder M, Carleton B. Pharmacogenomics and adverse drug reactions in children. Frontiers in Genetics. 2014; 5: 78.
  24. U. S. Department of Health and Human Services, Food and Drug Administration, Informed Consent Information Sheet, Guidance for IRBs, Clinical Investigators, and Sponsors, DRAFT GUIDANCE. July 2014. Available from URL: https://www.fda.gov/files/about%20fda/published/Informed-Consent-Information-Sheet%28Printer-Friendly%29.pdf. Date of the application: 05.05.2023.
  25. U. S. Department of Health and Human Services, Food and Drug Administration, Ethical Considerations for Clinical Investigations of Medical Products Involving Children Guidance for Industry, Sponsors, and IRBs; DRAFT GUIDANCE. September 2022. Available from URL: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/ethical-considerations-clinical-investigations-medical-products-involving-children Date of the application: 05.05.2023.
  26. U. S. Department of Health and Human Services, Food and Drug Administration, International Collaboration / Pediatric Cluster. Available from URL: https://www.fda.gov/science-research/pediatrics/international-collaboration-pediatric-cluster. Date of the application: 05.05.2023.
  27. Nicolas JM, Bouzom F, Hugues C. Oral drug absorption in pediatrics: the intestinal wall, its developmental changes and current tools for predictions. Biopharmaceutics & Drug Disposition. 2017; 38(3): 209–230.
  28. Ollivier C, Mulugeta YL, Ruggieri L, et al. Paediatric extrapolation: a necessary paradigm shift. British Journal of Clinical Pharmacology. 2019; 85(4): 675–679.
  29. Wang J, Avant D, Green D, et al. A survey of neonatal pharmacokinetic and pharmacodynamic studies in pediatric drug development. Clinical Pharmacology & Therapeutics. 2015; 98(3): 328–335.
  30. ICH E11. Available from URL: http://www.ich.org/fileadmin/ Public_Web_Site/ICH_Products/Guidelines/Efficacy/E11/Step4/ E11_Guideline.pdf. Date of the application: 05.05.2023.
  31. U. S. Department of Health and Human Services, Food and Drug Administration, General Clinical Pharmacology Considerations for Neonatal Studies for Drugs and Biological Products, Guidance for Industry. July 2022. Available from URL: https://www.fda. gov/regulatory-information/search-fda-guidance-documents/ general-clinical-pharmacology-considerations-neonatal-studiesdrugs-and-biological-products-guidance. Date of the application: 05.05.2023.
  32. US Food and Drug Administration. Medical Products for Newborns. Available from URL: https://www.fda.gov/ science-research/pediatrics/medical-products-newborns. Date of the application: 14.05.2023.
  33. Momper J, Mulugeta Y, Burckart G. Failed pediatric drug development trials. Clinical Pharmacology & Therapeutics. 2015; 98(3): 245–251.
  34. Weimer K, Gulewitsch MD, Schlarb AA. Placebo eff ects in children: a review. Pediatric Research. 2013; 74(1): 96–102.
  35. Simoens S, Cassiman D, Dooms M, et al. Orphan drugs for rare diseases: is it time to revisit their special market access status? Drugs. 2012; 72(11): 1437–1443.
  36. Ob osnovakh okhrany zdorov’ya grazhdan v Rossiyskoy Federatsii. Federal’nyy zakon ot 21.11.2011 № 323-FZ. Sayt Spravochno-pravovoy sistemy «Garant». Available from URL: https://base.garant.ru/12191967/ Date of the application: 05.05.2023. Russian.
  37. Arnold RJ, Bighash L, Bryon Nieto A, et al. The role of globalization in drug development and access to orphan drugs: orphan drug legislation in the US/EU and in Latin America. F1000Res. 2015; 4: 57.
  38. Bhattacharya I, Manukyan Z, Chan P. Making every subject count: a case study of drug development path for medication in a pediatric rare disease. Clinical Pharmacology & Therapeutics. 2016; 100(4): 330–332.